Mar 20, 2010

Genetic analysis of variation in transcription factor binding in yeast

Nature
Wei ZhengMichael Snyder

Abstract

Variation in transcriptional regulation is thought to be a major cause of phenotypic diversity. Although widespread differences in gene expression among individuals of a species have been observed, studies to examine the variability of transcription factor binding on a global scale have not been performed, and thus the extent and underlying genetic basis of transcription factor binding diversity is unknown. By mapping differences in transcription factor binding among individuals, here we present the genetic basis of such variation on a genome-wide scale. Whole-genome Ste12-binding profiles were determined using chromatin immunoprecipitation coupled with DNA sequencing in pheromone-treated cells of 43 segregants of a cross between two highly diverged yeast strains and their parental lines. We identified extensive Ste12-binding variation among individuals, and mapped underlying cis- and trans-acting loci responsible for such variation. We showed that most transcription factor binding variation is cis-linked, and that many variations are associated with polymorphisms residing in the binding motifs of Ste12 as well as those of several proposed Ste12 cofactors. We also identified two trans-factors, AMN1 and FLO8, that modulate Ste12...Continue Reading

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Mentioned in this Paper

Saccharomyces cerevisiae Proteins
Quantitative Trait Loci
Transcriptional Regulation
Cell Cycle Proteins
Genetic Analysis
Genetic Screening Method
Promoter
Gene Expression Regulation, Fungal
Chromatin Immunoprecipitation
Plasma Protein Binding Capacity

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